The proposed study concerns the organization of the myelin membrane and its alteration in disease. We are examining the metabolic turnover and the interrelationships of the three classes of myelin proteins. The basic and Folch-Lees proteins have been extensively studied, however, the data available are inconclusive due to limitations of current experimental procedures. The procedures we are currently using to study the proteins in myelin subfractions will provide definitive data. Recent work indicate that the two major proteins in the "Wolfgram" fraction are tubulin and filarin which are derived from the axon. The fractionation, isotopic, immunoradiometric, and affinity chromatographic techniques applied to the membrane proteins will also be used to study the metabolic turnover of tubulin, filarin, and the glial fibrillary acidic (GFAP) proteins. A comparison of the metabolic and chemical properties of the fibrous acidic proteins in the brain to the "Wolfgram" acidic proteins will aid in determining the origin of the "Wolfgram" proteins associated with myelin. While the etiology of many brain diseases is still unknown, the morphological and chemical alterations in terms of depletion or abnormal accumulations of proteins and lipids hve been well documented for many diseases, largely on the basis of examination of autopsy or biopsy material. Direct chemical measurements of proteins in the brain of living patients is not feasible except in the course of brain biopsy, but the use of body fluids (spinal fluid, blood, and urine) could well give crucial information for early diagnosis, prognosis, and management of patients with central nervous system disease provided highly specific and sensitive assays for brain proteins or antibodies to these proteins could be devised. The immunoradiometric assays we have (GFAP and Moore's S-100) and others we propose to develop may have immediate clinical diagnostic application.